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A Lesser Evil: Prophylactic Mastectomy for Women at High Risk for Breast Cancer

The University of Texas M. D. Anderson Cancer Center, Houston, TX

The identification of the BRCA1 and BRCA2 gene mutations was a milestone in the fight to eradicate breast cancer. We hoped we would soon be able to prevent not only hereditary breast and ovarian cancers (HBOC), but sporadic tumors as well. In this struggle, unfortunately, victories are rarely as sweeping as they first appear. It has been more than 10 years since genetic tests for HBOC became commercially available. A recent analysis of surveillance for women with familial breast cancer in Norway and the United Kingdom revealed that, once diagnosed with apparently early-stage breast cancer, BRCA2 carriers and women who tested negative for BRCA mutations had 5-year survival rates of 96% and 90% respectively, compared with only 70% for women carrying BRCA1 mutations.¹

How can we improve prevention for women at high risk of breast cancer? Surveillance can be enhanced by use of magnetic resonance imaging of the breasts.² Tamoxifen also reduces breast cancer risk in BRCA2 mutation carriers and the risk of contralateral second primaries in both BRCA2 and BRCA1 carriers,² but the intervention that most effectively prevents breast cancer is bilateral prophylactic mastectomy (BPM).^2,3 Bilateral prophylactic oophorectomy before age 40 and contralateral prophylactic mastectomy also reduce breast cancer risk substantially.

Women who are mutation carriers or have familial cancer are far more likely to have bilateral prophylactic oophorectomy than BPM.^2,3 At-risk women in the United States have one of the highest BPM rates (36%), with such surgery much less frequent among European women.² Factors predictive of choosing BPM include having a sister who had breast cancer,⁴ being a BRCA1/2 mutation carrier, having a personal history of breast cancer, being younger at the time of surgery than women who choose surveillance, and having high anxiety and exaggerated perceptions about risk of breast cancer.⁵ Women with young children may choose BPM to maximize their chances of long-term survival.⁶

BPM eliminates most or all erotic pleasure from breast caressing,⁷ and a sizable minority of women are surprised and upset by the complications of reconstructive surgery.^3,8 A number of researchers have investigated the emotional consequences of BPM beyond those specific drawbacks, trying to weigh both positive and negative impacts on women's lives.

This latest report from Brandberg et al⁹ in this issue of Journal of Clinical Oncology agrees well with previous studies, suggesting that changes in overall quality of life attributable to BPM are minor. Within this prospectively studied cohort, this outcome measure remained stable from before surgery to 1-year follow-up. Generalized anxiety decreased.^3,6,10 As in other surveys, women reported some problems with feeling less attractive or having sexual dysfunction. Brandberg et al surveyed only women with BPM. When other researchers compared women who had BPM or contralateral prophylactic mastectomy with women who chose surveillance, no differences were found between groups on these dimensions, suggesting that problems with body image or sexual function are related to women's at-risk status rather than to prophylactic surgery.^6,10,11 In fact, a recent survey using the Sexual Activity Questionnaire, the same instrument chosen by Brandberg et al, found that women at high risk of breast cancer had more sexual problems than healthy women, regardless of whether they were on a chemoprevention trial or had been offered risk-reducing surgery.¹² By comparison, women with advanced ovarian cancer had far more severe sexual dysfunction.

Brandberg et al⁹ found problems with body image in about half of their respondents. Approximately 20% of women in other BPM case series are distressed about body image or sexuality.^3,10,13 The discrepancy may reflect the way that Brandberg et al defined a problem. On items from the Body Image Scale, any response other than "not at all" was counted. If women responding "a little" are not counted as having a problem, the rate of self-consciousness falls from 48% to 7%. Only 11%, instead of 48%, of women feel less sexually attractive and 6%, instead of 44%, are dissatisfied with their scars.

Not only are women who choose BPM apt to be more distressed than women who choose surveillance, but distress levels at baseline remain unchanged by surgery at 1-year follow-up.^13,14 If women at risk for distress can be identified at baseline, they can be offered extra counseling. Researchers have already piloted a decision aid for BRCA mutation carriers that decreases conflict about whether to choose prophylactic surgery.¹⁵ In weighing options, it may also be helpful to remind women that the sexual and body image morbidity after BPM is far less severe than that associated with treatment for breast or ovarian cancer, particularly when chemotherapy is required.^12,16 If women remain distressed after surgery, 1-day workshops¹⁷ and problem-solving cognitive-behavioral therapy¹⁸ have shown promise in helping them to cope more effectively. Until we have less crude methods of cancer prevention, we should continue to identify women who are most distressed before surgery and refine our strategies to reduce their specific symptoms and concerns afterwards.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Moller P, Evans DG, Reis MM, et al: Surveillance for familial breast cancer: Differences in outcome according to BRCA mutation status. Int J Cancer 121:1017-1020, 2007[CrossRef][Medline]

2. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, et al: International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 122:2017-2022, 2008[CrossRef][Medline]

3. Lostumbo L, Carbine N, Wallace J, et al: Prophylactic mastectomy for the prevention of breast cancer. Oxford, United Kingdom, Cochrane Library, CD002748, 4, 2004

4. Metcalfe KA, Foulkes WD, Kim-Sing C, et al: Family history as a predictor of uptake of cancer preventive procedures by women with a BRCA1 or BRCA2 mutation. Clin Genet 73:474-479, 2008[Medline]

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6. Bresser PJC, Seynaeve C, Van Gool AR, et al: The course of distress in women at increased risk of breast and ovarian cancer due to an (identified) genetic susceptibility who opt for prophylactic mastectomy and/or salpingo-oophorectomy. Eur J Cancer 43:95-103, 2007[CrossRef][Medline]

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10. Geiger AM, Nekhlyudov L, Herrinton LJ, et al: Quality of life and body image after bilateral prophylactic mastectomy. Ann Surg Oncol 14:686-694, 2007[CrossRef][Medline]

11. Tercyak KP, Peshkin BN, Brogan BM, et al: Quality of life after contralateral prophylactic mastectomy in newly diagnosed high-risk breast cancer patients who underwent BRCA1/2 gene testing. J Clin Oncol 25:285-291, 2007[Abstract/Free Full Text]

12. Atkins L, Fallowfield LJ: Fallowfield's Sexual Activity Questionnaire in women with, without, and at risk of cancer. Menopause Int 13:103-109, 2007[Abstract/Free Full Text]

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14. Bresser PJC, Van Gool AR, Seynaeve C, et al: Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy? Ann Oncol 18:1641-1645, 2007[Abstract/Free Full Text]

15. Metcalfe KA, Poll A, O'Connor A, et al: Development and testing of a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. Clin Genet 72:208-217, 2007[CrossRef][Medline]

16. Schover LR: Reproductive complications and sexual dysfunction in cancer survivors, in Ganz PA (ed): Cancer Survivorship: Today and Tomorrow. New York, NY, Springer, 2007, pp 251-271

17. McKinnon W, Naud S, Ashikaga T, et al: Results of an intervention for individuals and families with BRCA mutations: A model for providing medical updates and psychosocial support following genetic testing. J Genet Couns 16:433-456, 2007[CrossRef][Medline]

18. McInerney-Leo A, Biesecker BB, Hadley DW, et al: BRCA1/2 testing in hereditary breast and ovarian cancer families: Effectiveness of problem-solving training as a counseling intervention. Am J Med Genet A 130A:221-227, 2004

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